Liraglutide attenuates obese-associated breast cancer cell proliferation via inhibiting PI3K/Akt/mTOR signaling

Alaa Alanteet1, Hala Attia1, Musaed Alfayez2

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Insights

Liraglutide (LGT) exhibits anti-proliferative and pro-apoptotic effects on breast cancer cells in obese individuals. This action suppresses survival pathways, independent of the AMPK/SIRT1 pathway.

Area of Science:

  • Oncology
  • Metabolic Syndrome
  • Cell Biology

Background:

  • Obesity is linked to increased breast cancer (BC) risk and progression.
  • Adipose-derived stem cells (ADSCs) in obesity can influence BC cell behavior.
  • Liraglutide (LGT) is a GLP-1 receptor agonist with potential anti-cancer properties.

Purpose of the Study:

  • To investigate the effects of LGT on MCF-7 breast cancer cells cultured in a medium from obese ADSCs.
  • To determine LGT's impact on cell proliferation, apoptosis, and migration.
  • To explore LGT's influence on the PI3K/Akt/mTOR/AMPK pathway and adipokine production.

Main Methods:

  • MCF-7 cells were cultured in conditioned medium (CM) from obese ADSCs and treated with LGT.
  • Cell proliferation, apoptosis, and migration were assessed using alamarBlue, annexin V staining, and scratch assays.
  • Protein levels of PI3K, Akt, mTOR, and AMPK were analyzed via immunoblotting; adipokine levels were measured using RT-PCR.

Main Results:

  • LGT demonstrated anti-proliferative, pro-apoptotic, and anti-migratory effects on MCF-7 cells.
  • LGT significantly inhibited the PI3K/Akt/mTOR survival pathway in MCF-7 cells.
  • LGT's effects were independent of the AMPK/SIRT1 pathway in ADSCs or AMPK in BC cells.

Conclusions:

  • LGT exerts anti-cancer effects on breast cancer cells in obese conditions by suppressing key survival pathways.
  • The anti-proliferative and apoptotic effects of LGT are mediated through the PI3K/Akt/mTOR pathway.
  • The study highlights LGT's potential as a therapeutic agent in obese patients with breast cancer, independent of AMPK/SIRT1 signaling.

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